OntoTag - A Linguistic and Ontological Annotation Model Suitable for the Semantic Web

OntoTag - A Linguistic and Ontological Annotation Model Suitable for the Semantic Web 1. INTRODUCTION. LINGUISTIC TOOLS AND ANNOTATIONS: THEIR LIGHTS AND SHADOWS Computational Linguistics is already a consolidated research area. It builds upon the results of other two major ones, namely Linguistics and Computer Science and Engineering, and it aims at developing computational models of human language (or natural language, as it is termed in this area). Possibly, its most well-known applications are the different tools developed so far for processing human language, such as machine translation systems and speech recognizers or dictation programs. These tools for processing human language are commonly referred to as linguistic tools. Apart from the examples mentioned above, there are also other types of linguistic tools that perhaps are not so well-known, but on which most of the other applications of Computational Linguistics are built. These other types of linguistic tools comprise POS taggers, natural language parsers and semantic taggers, amongst others. All of them can be termed linguistic annotation tools. Linguistic annotation tools are important assets. In fact, POS and semantic taggers (and, to a lesser extent, also natural language parsers) have become critical resources for the computer applications that process natural language. Hence, any computer application that has to analyse a text automatically and ‘intelligently’ will include at least a module for POS tagging. The more an application needs to ‘understand’ the meaning of the text it processes, the more linguistic tools and/or modules it will incorporate and integrate. However, linguistic annotation tools have still some limitations, which can be summarised as follows: 1. Normally, they perform annotations only at a certain linguistic level (that is, Morphology, Syntax, Semantics, etc.). 2. They usually introduce a certain rate of errors and ambiguities when tagging. This error rate ranges from 10 percent up to 50 percent of the units annotated for unrestricted, general texts. 3. Their annotations are most frequently formulated in terms of an annotation schema designed and implemented ad hoc. A priori, it seems that the interoperation and the integration of several linguistic tools into an appropriate software architecture could most likely solve the limitations stated in (1). Besides, integrating several linguistic annotation tools and making them interoperate could also minimise the limitation stated in (2). Nevertheless, in the latter case, all these tools should produce annotations for a common level, which would have to be combined in order to correct their corresponding errors and inaccuracies. Yet, the limitation stated in (3) prevents both types of integration and interoperation from being easily achieved. In addition, most high-level annotation tools rely on other lower-level annotation tools and their outputs to generate their own ones. For example, sense-tagging tools (operating at the semantic level) often use POS taggers (operating at a lower level, i.e., the morphosyntactic) to identify the grammatical category of the word or lexical unit they are annotating. Accordingly, if a faulty or inaccurate low-level annotation tool is to be used by other higher-level one in its process, the errors and inaccuracies of the former should be minimised in advance. Otherwise, these errors and inaccuracies would be transferred to (and even magnified in) the annotations of the high-level annotation tool. Therefore, it would be quite useful to find a way to (i) correct or, at least, reduce the errors and the inaccuracies of lower-level linguistic tools; (ii) unify the annotation schemas of different linguistic annotation tools or, more generally speaking, make these tools (as well as their annotations) interoperate. Clearly, solving (i) and (ii) should ease the automatic annotation of web pages by means of linguistic tools, and their transformation into Semantic Web pages (Berners-Lee, Hendler and Lassila, 2001). Yet, as stated above, (ii) is a type of interoperability problem. There again, ontologies (Gruber, 1993; Borst, 1997) have been successfully applied thus far to solve several interoperability problems. Hence, ontologies should help solve also the problems and limitations of linguistic annotation tools aforementioned. Thus, to summarise, the main aim of the present work was to combine somehow these separated approaches, mechanisms and tools for annotation from Linguistics and Ontological Engineering (and the Semantic Web) in a sort of hybrid (linguistic and ontological) annotation model, suitable for both areas. This hybrid (semantic) annotation model should (a) benefit from the advances, models, techniques, mechanisms and tools of these two areas; (b) minimise (and even solve, when possible) some of the problems found in each of them; and (c) be suitable for the Semantic Web. The concrete goals that helped attain this aim are presented in the following section. 2. GOALS OF THE PRESENT WORK As mentioned above, the main goal of this work was to specify a hybrid (that is, linguistically-motivated and ontology-based) model of annotation suitable for the Semantic Web (i.e. it had to produce a semantic annotation of web page contents). This entailed that the tags included in the annotations of the model had to (1) represent linguistic concepts (or linguistic categories, as they are termed in ISO/DCR (2008)), in order for this model to be linguistically-motivated; (2) be ontological terms (i.e., use an ontological vocabulary), in order for the model to be ontology-based; and (3) be structured (linked) as a collection of ontology-based triples, as in the usual Semantic Web languages (namely RDF(S) and OWL), in order for the model to be considered suitable for the Semantic Web. Besides, to be useful for the Semantic Web, this model should provide a way to automate the annotation of web pages. As for the present work, this requirement involved reusing the linguistic annotation tools purchased by the OEG research group (http://www.oeg-upm.net), but solving beforehand (or, at least, minimising) some of their limitations. Therefore, this model had to minimise these limitations by means of the integration of several linguistic annotation tools into a common architecture. Since this integration required the interoperation of tools and their annotations, ontologies were proposed as the main technological component to make them effectively interoperate. From the very beginning, it seemed that the formalisation of the elements and the knowledge underlying linguistic annotations within an appropriate set of ontologies would be a great step forward towards the formulation of such a model (henceforth referred to as OntoTag). Obviously, first, to combine the results of the linguistic annotation tools that operated at the same level, their annotation schemas had to be unified (or, preferably, standardised) in advance. This entailed the unification (id. standardisation) of their tags (both their representation and their meaning), and their format or syntax. Second, to merge the results of the linguistic annotation tools operating at different levels, their respective annotation schemas had to be (a) made interoperable and (b) integrated. And third, in order for the resulting annotations to suit the Semantic Web, they had to be specified by means of an ontology-based vocabulary, and structured by means of ontology-based triples, as hinted above. Therefore, a new annotation scheme had to be devised, based both on ontologies and on this type of triples, which allowed for the combination and the integration of the annotations of any set of linguistic annotation tools. This annotation scheme was considered a fundamental part of the model proposed here, and its development was, accordingly, another major objective of the present work. All these goals, aims and objectives could be re-stated more clearly as follows: Goal 1: Development of a set of ontologies for the formalisation of the linguistic knowledge relating linguistic annotation. Sub-goal 1.1: Ontological formalisation of the EAGLES (1996a; 1996b) de facto standards for morphosyntactic and syntactic annotation, in a way that helps respect the triple structure recommended for annotations in these works (which is isomorphic to the triple structures used in the context of the Semantic Web). Sub-goal 1.2: Incorporation into this preliminary ontological formalisation of other existing standards and standard proposals relating the levels mentioned above, such as those currently under development within ISO/TC 37 (the ISO Technical Committee dealing with Terminology, which deals also with linguistic resources and annotations). Sub-goal 1.3: Generalisation and extension of the recommendations in EAGLES (1996a; 1996b) and ISO/TC 37 to the semantic level, for which no ISO/TC 37 standards have been developed yet. Sub-goal 1.4: Ontological formalisation of the generalisations and/or extensions obtained in the previous sub-goal as generalisations and/or extensions of the corresponding ontology (or ontologies). Sub-goal 1.5: Ontological formalisation of the knowledge required to link, combine and unite the knowledge represented in the previously developed ontology (or ontologies). Goal 2: Development of OntoTag’s annotation scheme, a standard-based abstract scheme for the hybrid (linguistically-motivated and ontological-based) annotation of texts. Sub-goal 2.1: Development of the standard-based morphosyntactic annotation level of OntoTag’s scheme. This level should include, and possibly extend, the recommendations of EAGLES (1996a) and also the recommendations included in the ISO/MAF (2008) standard draft. Sub-goal 2.2: Development of the standard-based syntactic annotation level of the hybrid abstract scheme. This level should include, and possibly extend, the recommendations of EAGLES (1996b) and the ISO/SynAF (2010) standard draft. Sub-goal 2.3: Development of the standard-based semantic annotation level of OntoTag’s (abstract) scheme. Sub-goal 2.4: Development of the mechanisms for a convenient integration of the three annotation levels already mentioned. These mechanisms should take into account the recommendations included in the ISO/LAF (2009) standard draft. Goal 3: Design of OntoTag’s (abstract) annotation architecture, an abstract architecture for the hybrid (semantic) annotation of texts (i) that facilitates the integration and interoperation of different linguistic annotation tools, and (ii) whose results comply with OntoTag’s annotation scheme. Sub-goal 3.1: Specification of the decanting processes that allow for the classification and separation, according to their corresponding levels, of the results of the linguistic tools annotating at several different levels. Sub-goal 3.2: Specification of the standardisation processes that allow (a) complying with the standardisation requirements of OntoTag’s annotation scheme, as well as (b) combining the results of those linguistic tools that share some level of annotation. Sub-goal 3.3: Specification of the merging processes that allow for the combination of the output annotations and the interoperation of those linguistic tools that share some level of annotation. Sub-goal 3.4: Specification of the merge processes that allow for the integration of the results and the interoperation of those tools performing their annotations at different levels. Goal 4: Generation of OntoTagger’s schema, a concrete instance of OntoTag’s abstract scheme for a concrete set of linguistic annotations. These linguistic annotations result from the tools and the resources available in the research group, namely • Bitext’s DataLexica (http://www.bitext.com/EN/datalexica.asp), • LACELL’s (POS) tagger (http://www.um.es/grupos/grupo-lacell/quees.php), • Connexor’s FDG (http://www.connexor.eu/technology/machinese/glossary/fdg/), and • EuroWordNet (Vossen et al., 1998). This schema should help evaluate OntoTag’s underlying hypotheses, stated below. Consequently, it should implement, at least, those levels of the abstract scheme dealing with the annotations of the set of tools considered in this implementation. This includes the morphosyntactic, the syntactic and the semantic levels. Goal 5: Implementation of OntoTagger’s configuration, a concrete instance of OntoTag’s abstract architecture for this set of linguistic tools and annotations. This configuration (1) had to use the schema generated in the previous goal; and (2) should help support or refute the hypotheses of this work as well (see the next section). Sub-goal 5.1: Implementation of the decanting processes that facilitate the classification and separation of the results of those linguistic resources that provide annotations at several different levels (on the one hand, LACELL’s tagger operates at the morphosyntactic level and, minimally, also at the semantic level; on the other hand, FDG operates at the morphosyntactic and the syntactic levels and, minimally, at the semantic level as well). Sub-goal 5.2: Implementation of the standardisation processes that allow (i) specifying the results of those linguistic tools that share some level of annotation according to the requirements of OntoTagger’s schema, as well as (ii) combining these shared level results. In particular, all the tools selected perform morphosyntactic annotations and they had to be conveniently combined by means of these processes. Sub-goal 5.3: Implementation of the merging processes that allow for the combination (and possibly the improvement) of the annotations and the interoperation of the tools that share some level of annotation (in particular, those relating the morphosyntactic level, as in the previous sub-goal). Sub-goal 5.4: Implementation of the merging processes that allow for the integration of the different standardised and combined annotations aforementioned, relating all the levels considered. Sub-goal 5.5: Improvement of the semantic level of this configuration by adding a named entity recognition, (sub-)classification and annotation subsystem, which also uses the named entities annotated to populate a domain ontology, in order to provide a concrete application of the present work in the two areas involved (the Semantic Web and Corpus Linguistics). 3. MAIN RESULTS: ASSESSMENT OF ONTOTAG’S UNDERLYING HYPOTHESES The model developed in the present thesis tries to shed some light on (i) whether linguistic annotation tools can effectively interoperate; (ii) whether their results can be combined and integrated; and, if they can, (iii) how they can, respectively, interoperate and be combined and integrated. Accordingly, several hypotheses had to be supported (or rejected) by the development of the OntoTag model and OntoTagger (its implementation). The hypotheses underlying OntoTag are surveyed below. Only one of the hypotheses (H.6) was rejected; the other five could be confirmed. H.1 The annotations of different levels (or layers) can be integrated into a sort of overall, comprehensive, multilayer and multilevel annotation, so that their elements can complement and refer to each other. • CONFIRMED by the development of: o OntoTag’s annotation scheme, o OntoTag’s annotation architecture, o OntoTagger’s (XML, RDF, OWL) annotation schemas, o OntoTagger’s configuration. H.2 Tool-dependent annotations can be mapped onto a sort of tool-independent annotations and, thus, can be standardised. • CONFIRMED by means of the standardisation phase incorporated into OntoTag and OntoTagger for the annotations yielded by the tools. H.3 Standardisation should ease: H.3.1: The interoperation of linguistic tools. H.3.2: The comparison, combination (at the same level and layer) and integration (at different levels or layers) of annotations. • H.3 was CONFIRMED by means of the development of OntoTagger’s ontology-based configuration: o Interoperation, comparison, combination and integration of the annotations of three different linguistic tools (Connexor’s FDG, Bitext’s DataLexica and LACELL’s tagger); o Integration of EuroWordNet-based, domain-ontology-based and named entity annotations at the semantic level. o Integration of morphosyntactic, syntactic and semantic annotations. H.4 Ontologies and Semantic Web technologies (can) play a crucial role in the standardisation of linguistic annotations, by providing consensual vocabularies and standardised formats for annotation (e.g., RDF triples). • CONFIRMED by means of the development of OntoTagger’s RDF-triple-based annotation schemas. H.5 The rate of errors introduced by a linguistic tool at a given level, when annotating, can be reduced automatically by contrasting and combining its results with the ones coming from other tools, operating at the same level. However, these other tools might be built following a different technological (stochastic vs. rule-based, for example) or theoretical (dependency vs. HPS-grammar-based, for instance) approach. • CONFIRMED by the results yielded by the evaluation of OntoTagger. H.6 Each linguistic level can be managed and annotated independently. • REJECTED: OntoTagger’s experiments and the dependencies observed among the morphosyntactic annotations, and between them and the syntactic annotations. In fact, Hypothesis H.6 was already rejected when OntoTag’s ontologies were developed. We observed then that several linguistic units stand on an interface between levels, belonging thereby to both of them (such as morphosyntactic units, which belong to both the morphological level and the syntactic level). Therefore, the annotations of these levels overlap and cannot be handled independently when merged into a unique multileveled annotation. 4. OTHER MAIN RESULTS AND CONTRIBUTIONS First, interoperability is a hot topic for both the linguistic annotation community and the whole Computer Science field. The specification (and implementation) of OntoTag’s architecture for the combination and integration of linguistic (annotation) tools and annotations by means of ontologies shows a way to make these different linguistic annotation tools and annotations interoperate in practice. Second, as mentioned above, the elements involved in linguistic annotation were formalised in a set (or network) of ontologies (OntoTag’s linguistic ontologies). • On the one hand, OntoTag’s network of ontologies consists of − The Linguistic Unit Ontology (LUO), which includes a mostly hierarchical formalisation of the different types of linguistic elements (i.e., units) identifiable in a written text; − The Linguistic Attribute Ontology (LAO), which includes also a mostly hierarchical formalisation of the different types of features that characterise the linguistic units included in the LUO; − The Linguistic Value Ontology (LVO), which includes the corresponding formalisation of the different values that the attributes in the LAO can take; − The OIO (OntoTag’s Integration Ontology), which  Includes the knowledge required to link, combine and unite the knowledge represented in the LUO, the LAO and the LVO;  Can be viewed as a knowledge representation ontology that describes the most elementary vocabulary used in the area of annotation. • On the other hand, OntoTag’s ontologies incorporate the knowledge included in the different standards and recommendations for linguistic annotation released so far, such as those developed within the EAGLES and the SIMPLE European projects or by the ISO/TC 37 committee: − As far as morphosyntactic annotations are concerned, OntoTag’s ontologies formalise the terms in the EAGLES (1996a) recommendations and their corresponding terms within the ISO Morphosyntactic Annotation Framework (ISO/MAF, 2008) standard; − As for syntactic annotations, OntoTag’s ontologies incorporate the terms in the EAGLES (1996b) recommendations and their corresponding terms within the ISO Syntactic Annotation Framework (ISO/SynAF, 2010) standard draft; − Regarding semantic annotations, OntoTag’s ontologies generalise and extend the recommendations in EAGLES (1996a; 1996b) and, since no stable standards or standard drafts have been released for semantic annotation by ISO/TC 37 yet, they incorporate the terms in SIMPLE (2000) instead; − The terms coming from all these recommendations and standards were supplemented by those within the ISO Data Category Registry (ISO/DCR, 2008) and also of the ISO Linguistic Annotation Framework (ISO/LAF, 2009) standard draft when developing OntoTag’s ontologies. Third, we showed that the combination of the results of tools annotating at the same level can yield better results (both in precision and in recall) than each tool separately. In particular, 1. OntoTagger clearly outperformed two of the tools integrated into its configuration, namely DataLexica and FDG in all the combination sub-phases in which they overlapped (i.e. POS tagging, lemma annotation and morphological feature annotation). As far as the remaining tool is concerned, i.e. LACELL’s tagger, it was also outperformed by OntoTagger in POS tagging and lemma annotation, and it did not behave better than OntoTagger in the morphological feature annotation layer. 2. As an immediate result, this implies that a) This type of combination architecture configurations can be applied in order to improve significantly the accuracy of linguistic annotations; and b) Concerning the morphosyntactic level, this could be regarded as a way of constructing more robust and more accurate POS tagging systems. Fourth, Semantic Web annotations are usually performed by humans or else by machine learning systems. Both of them leave much to be desired: the former, with respect to their annotation rate; the latter, with respect to their (average) precision and recall. In this work, we showed how linguistic tools can be wrapped in order to annotate automatically Semantic Web pages using ontologies. This entails their fast, robust and accurate semantic annotation. As a way of example, as mentioned in Sub-goal 5.5, we developed a particular OntoTagger module for the recognition, classification and labelling of named entities, according to the MUC and ACE tagsets (Chinchor, 1997; Doddington et al., 2004). These tagsets were further specified by means of a domain ontology, namely the Cinema Named Entities Ontology (CNEO). This module was applied to the automatic annotation of ten different web pages containing cinema reviews (that is, around 5000 words). In addition, the named entities annotated with this module were also labelled as instances (or individuals) of the classes included in the CNEO and, then, were used to populate this domain ontology. • The statistical results obtained from the evaluation of this particular module of OntoTagger can be summarised as follows. On the one hand, as far as recall (R) is concerned, (R.1) the lowest value was 76,40% (for file 7); (R.2) the highest value was 97, 50% (for file 3); and (R.3) the average value was 88,73%. On the other hand, as far as the precision rate (P) is concerned, (P.1) its minimum was 93,75% (for file 4); (R.2) its maximum was 100% (for files 1, 5, 7, 8, 9, and 10); and (R.3) its average value was 98,99%. • These results, which apply to the tasks of named entity annotation and ontology population, are extraordinary good for both of them. They can be explained on the basis of the high accuracy of the annotations provided by OntoTagger at the lower levels (mainly at the morphosyntactic level). However, they should be conveniently qualified, since they might be too domain- and/or language-dependent. It should be further experimented how our approach works in a different domain or a different language, such as French, English, or German. • In any case, the results of this application of Human Language Technologies to Ontology Population (and, accordingly, to Ontological Engineering) seem very promising and encouraging in order for these two areas to collaborate and complement each other in the area of semantic annotation. Fifth, as shown in the State of the Art of this work, there are different approaches and models for the semantic annotation of texts, but all of them focus on a particular view of the semantic level. Clearly, all these approaches and models should be integrated in order to bear a coherent and joint semantic annotation level. OntoTag shows how (i) these semantic annotation layers could be integrated together; and (ii) they could be integrated with the annotations associated to other annotation levels. Sixth, we identified some recommendations, best practices and lessons learned for annotation standardisation, interoperation and merge. They show how standardisation (via ontologies, in this case) enables the combination, integration and interoperation of different linguistic tools and their annotations into a multilayered (or multileveled) linguistic annotation, which is one of the hot topics in the area of Linguistic Annotation. And last but not least, OntoTag’s annotation scheme and OntoTagger’s annotation schemas show a way to formalise and annotate coherently and uniformly the different units and features associated to the different levels and layers of linguistic annotation. This is a great scientific step ahead towards the global standardisation of this area, which is the aim of ISO/TC 37 (in particular, Subcommittee 4, dealing with the standardisation of linguistic annotations and resources).

Integrative bioinformatics for functional genorne annotation:trawling for G protein-coupled receptors

G protein-coupled receptors (GPCR) are amongst the best studied and most functionally diverse types of cell-surface protein. The importance of GPCRs as mediates or cell function and organismal developmental underlies their involvement in key physiological roles and their prominence as targets for pharmacological therapeutics. In this review, we highlight the requirement for integrated protocols which underline the different perspectives offered by different sequence analysis methods. BLAST and FastA offer broad brush strokes. Motif-based search methods add the fine detail. Structural modelling offers another perspective which allows us to elucidate the physicochemical properties that underlie ligand binding. Together, these different views provide a more informative and a more detailed picture of GPCR structure and function. Many GPCRs remain orphan receptors with no identified ligand, yet as computer-driven functional genomics starts to elaborate their functions, a new understanding of their roles in cell and developmental biology will follow.

Iis--integrated Interactome System: A Web-based Platform For The Annotation, Analysis And Visualization Of Protein-metabolite-gene-drug Interactions By Integrating A Variety Of Data Sources And Tools.

High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.

The 2008 update of the Aspergillus nidulans genome annotation: A community effort

The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.

NOVA ANOTAÇÃO SINTÉTICA, NUMA PERSPECTIVA DE DIREITO PÚBLICO, AINDA AO ACÓRDÃO 212/95, DO TRIBUNAL CONSTITUCIONAL (PORTUGUÊS), DE 20.04.1995 - O DEVER FUNDAMENTAL DE EXISTIR NA LEI EM VIGOR UMA RESPONSABILIDADE CRIMINAL DAS "PESSOAS COLECTIVAS" (OU "PESSOAS JURÍDICAS") E A CONSTITUIÇÃO DA REPÚBLICA PORTUGUESA, V.G. O CASO DO ART. 7º DO REGIME GERAL DAS INFRACÇÕES TRIBUTÁRIAS E DO ART. 3.º DO REGIME DAS INFRACÇÕES ANTIECONÓMICAS E CONTRA A SAÚDE PÚBLICA

Resumo: 1 – Sumário do Acórdão do Tribunal Constitucional n.º 212/1995, de 20 de Abril; 2 – Parte principal do Acórdão do Tribunal Constitucional n.º 212/1995, de 20 de Abril: cfr. http://www.tribunalconstitucional.pt/tc/acordaos/19950212.html , 18 de Maio de 2012; 3 – Anotação sintética; 3.1 – Introdução à anotação sintética e suas características neste caso concreto; 4 – O RIAECSP (Regime das Infracções Anti-Económicas e Contra a Saúde Pública) e a responsabilidade criminal das pessoas colectivas e equiparadas, prevista no seu art. 3.º; 5 – Societas delinquere non potest?; 6 – Breves traços históricos do brocardo societas delinquere non potest; 7 - Alguns dos marcos relevantes na Doutrina penal portuguesa recente acerca da responsabilidade penal das organizações, entes colectivos, pessoas colectivas, pessoas jurídicas; 8 - Os art.os 12.º/2 e 2.º da CRP e a Responsabilidade Criminal dos Entes Colectivos, pessoas jurídicas; 9 - O art. 29.º/5 da CRP - ou o princípio non bis in idem - e a responsabilidade criminal das organizações, dos entes colectivos, das pessoas colectivas; 10 – Conclusões. § Summary: 1 - Summary Judgment of the Constitutional Court No. 212/1995 of 20 April; 2 - The main part of the Constitutional Court Ruling No. 212/1995 of 20 April: cfr. http://www.tribunalconstitucional.pt/tc/acordaos/19950212.html, May 18, 2012; 3 - short annotation; 3.1 - Introduction to synthetic note and its features in this particular case; 4 - The RIAECSP (Status of Anti-Economic Offences and Against Public Health) and the criminal liability of companies and similar persons, provided for in his art. 3; 5 - delinquere Societas non potest ?; 6 - Brief historical traces of societas aphorism delinquere non potest; 7 - Some of the important milestones in recent Portuguese criminal Doctrine about the criminal liability of organizations, public entities, legal persons, legal entities; 8 - art.os 12/2 and 2 of CRP and Criminal Responsibility of loved Collective, legal entities; 9 - Art. 29/5 CRP - or the principle of non bis in idem - and the criminal liability of organizations, collective entities, of legal persons; 10 - Conclusions.

Gesture based interface for image annotation

Dissertação apresentada para obtenção do Grau de Mestre em Engenharia Informática pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

MyHits: a new interactive resource for protein annotation and domain identification.

The MyHits web server (http://myhits.isb-sib.ch) is a new integrated service dedicated to the annotation of protein sequences and to the analysis of their domains and signatures. Guest users can use the system anonymously, with full access to (i) standard bioinformatics programs (e.g. PSI-BLAST, ClustalW, T-Coffee, Jalview); (ii) a large number of protein sequence databases, including standard (Swiss-Prot, TrEMBL) and locally developed databases (splice variants); (iii) databases of protein motifs (Prosite, Interpro); (iv) a precomputed list of matches ('hits') between the sequence and motif databases. All databases are updated on a weekly basis and the hit list is kept up to date incrementally. The MyHits server also includes a new collection of tools to generate graphical representations of pairwise and multiple sequence alignments including their annotated features. Free registration enables users to upload their own sequences and motifs to private databases. These are then made available through the same web interface and the same set of analytical tools. Registered users can manage their own sequences and annotations using only web tools and freeze their data in their private database for publication purposes.

HAMAP in 2015: updates to the protein family classification and annotation system.

HAMAP (High-quality Automated and Manual Annotation of Proteins-available at http://hamap.expasy.org/) is a system for the automatic classification and annotation of protein sequences. HAMAP provides annotation of the same quality and detail as UniProtKB/Swiss-Prot, using manually curated profiles for protein sequence family classification and expert curated rules for functional annotation of family members. HAMAP data and tools are made available through our website and as part of the UniRule pipeline of UniProt, providing annotation for millions of unreviewed sequences of UniProtKB/TrEMBL. Here we report on the growth of HAMAP and updates to the HAMAP system since our last report in the NAR Database Issue of 2013. We continue to augment HAMAP with new family profiles and annotation rules as new protein families are characterized and annotated in UniProtKB/Swiss-Prot; the latest version of HAMAP (as of 3 September 2014) contains 1983 family classification profiles and 1998 annotation rules (up from 1780 and 1720). We demonstrate how the complex logic of HAMAP rules allows for precise annotation of individual functional variants within large homologous protein families. We also describe improvements to our web-based tool HAMAP-Scan which simplify the classification and annotation of sequences, and the incorporation of an improved sequence-profile search algorithm.

EGASP: the human ENCODE Genome Annotation Assessment Project

Background: We present the results of EGASP, a community experiment to assess the state-ofthe-art in genome annotation within the ENCODE regions, which span 1% of the human genomesequence. The experiment had two major goals: the assessment of the accuracy of computationalmethods to predict protein coding genes; and the overall assessment of the completeness of thecurrent human genome annotations as represented in the ENCODE regions. For thecomputational prediction assessment, eighteen groups contributed gene predictions. Weevaluated these submissions against each other based on a ‘reference set’ of annotationsgenerated as part of the GENCODE project. These annotations were not available to theprediction groups prior to the submission deadline, so that their predictions were blind and anexternal advisory committee could perform a fair assessment.Results: The best methods had at least one gene transcript correctly predicted for close to 70%of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into accountalternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotidelevel, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programsrelying on mRNA and protein sequences were the most accurate in reproducing the manuallycurated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could beverified.Conclusions: This is the first such experiment in human DNA, and we have followed thestandards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe theresults presented here contribute to the value of ongoing large-scale annotation projects and shouldguide further experimental methods when being scaled up to the entire human genome sequence.

GENCODE: the reference human genome annotation for The ENCODE Project.

The GENCODE Consortium aims to identify all gene features in the human genome using a combination of computational analysis, manual annotation, and experimental validation. Since the first public release of this annotation data set, few new protein-coding loci have been added, yet the number of alternative splicing transcripts annotated has steadily increased. The GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq. It also has the most comprehensive annotation of long noncoding RNA (lncRNA) loci publicly available with the predominant transcript form consisting of two exons. We have examined the completeness of the transcript annotation and found that 35% of transcriptional start sites are supported by CAGE clusters and 62% of protein-coding genes have annotated polyA sites. Over one-third of GENCODE protein-coding genes are supported by peptide hits derived from mass spectrometry spectra submitted to Peptide Atlas. New models derived from the Illumina Body Map 2.0 RNA-seq data identify 3689 new loci not currently in GENCODE, of which 3127 consist of two exon models indicating that they are possibly unannotated long noncoding loci. GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers.

The UniProt-GO Annotation database in 2011.

The GO annotation dataset provided by the UniProt Consortium (GOA: http://www.ebi.ac.uk/GOA) is a comprehensive set of evidenced-based associations between terms from the Gene Ontology resource and UniProtKB proteins. Currently supplying over 100 million annotations to 11 million proteins in more than 360,000 taxa, this resource has increased 2-fold over the last 2 years and has benefited from a wealth of checks to improve annotation correctness and consistency as well as now supplying a greater information content enabled by GO Consortium annotation format developments. Detailed, manual GO annotations obtained from the curation of peer-reviewed papers are directly contributed by all UniProt curators and supplemented with manual and electronic annotations from 36 model organism and domain-focused scientific resources. The inclusion of high-quality, automatic annotation predictions ensures the UniProt GO annotation dataset supplies functional information to a wide range of proteins, including those from poorly characterized, non-model organism species. UniProt GO annotations are freely available in a range of formats accessible by both file downloads and web-based views. In addition, the introduction of a new, normalized file format in 2010 has made for easier handling of the complete UniProt-GOA data set.

EGASP: the human ENCODE Genome Annotation Assessment Project.

BACKGROUND: We present the results of EGASP, a community experiment to assess the state-of-the-art in genome annotation within the ENCODE regions, which span 1% of the human genome sequence. The experiment had two major goals: the assessment of the accuracy of computational methods to predict protein coding genes; and the overall assessment of the completeness of the current human genome annotations as represented in the ENCODE regions. For the computational prediction assessment, eighteen groups contributed gene predictions. We evaluated these submissions against each other based on a 'reference set' of annotations generated as part of the GENCODE project. These annotations were not available to the prediction groups prior to the submission deadline, so that their predictions were blind and an external advisory committee could perform a fair assessment. RESULTS: The best methods had at least one gene transcript correctly predicted for close to 70% of the annotated genes. Nevertheless, the multiple transcript accuracy, taking into account alternative splicing, reached only approximately 40% to 50% accuracy. At the coding nucleotide level, the best programs reached an accuracy of 90% in both sensitivity and specificity. Programs relying on mRNA and protein sequences were the most accurate in reproducing the manually curated annotations. Experimental validation shows that only a very small percentage (3.2%) of the selected 221 computationally predicted exons outside of the existing annotation could be verified. CONCLUSION: This is the first such experiment in human DNA, and we have followed the standards established in a similar experiment, GASP1, in Drosophila melanogaster. We believe the results presented here contribute to the value of ongoing large-scale annotation projects and should guide further experimental methods when being scaled up to the entire human genome sequence.

EGASP: the human ENCODE Genome Annotation Assessment Project

Background: Non-long terminal repeat (non-LTR) retrotransposons have contributed to shaping the structure and function of genomes. In silico and experimental approaches have been used to identify the non-LTR elements of the urochordate Ciona intestinalis. Knowledge of the types and abundance of non-LTR elements in urochordates is a key step in understanding their contribution to the structure and function of vertebrate genomes. Results: Consensus elements phylogenetically related to the I, LINE1, LINE2, LOA and R2 elements of the 14 eukaryotic non-LTR clades are described from C. intestinalis. The ascidian elements showed conservation of both the reverse transcriptase coding sequence and the overall structural organization seen in each clade. The apurinic/apyrimidinic endonuclease and nucleic-acid-binding domains encoded upstream of the reverse transcriptase, and the RNase H and the restriction enzyme-like endonuclease motifs encoded downstream of the reverse transcriptase were identified in the corresponding Ciona families. Conclusions: The genome of C. intestinalis harbors representatives of at least five clades of non-LTR retrotransposons. The copy number per haploid genome of each element is low, less than 100, far below the values reported for vertebrate counterparts but within the range for protostomes. Genomic and sequence analysis shows that the ascidian non-LTR elements are unmethylated and flanked by genomic segments with a gene density lower than average for the genome. The analysis provides valuable data for understanding the evolution of early chordate genomes and enlarges the view on the distribution of the non-LTR retrotransposons in eukaryotes.

GENCODE: producing a reference annotation for ENCODE.

BACKGROUND: The GENCODE consortium was formed to identify and map all protein-coding genes within the ENCODE regions. This was achieved by a combination of initial manual annotation by the HAVANA team, experimental validation by the GENCODE consortium and a refinement of the annotation based on these experimental results. RESULTS: The GENCODE gene features are divided into eight different categories of which only the first two (known and novel coding sequence) are confidently predicted to be protein-coding genes. 5' rapid amplification of cDNA ends (RACE) and RT-PCR were used to experimentally verify the initial annotation. Of the 420 coding loci tested, 229 RACE products have been sequenced. They supported 5' extensions of 30 loci and new splice variants in 50 loci. In addition, 46 loci without evidence for a coding sequence were validated, consisting of 31 novel and 15 putative transcripts. We assessed the comprehensiveness of the GENCODE annotation by attempting to validate all the predicted exon boundaries outside the GENCODE annotation. Out of 1,215 tested in a subset of the ENCODE regions, 14 novel exon pairs were validated, only two of them in intergenic regions. CONCLUSION: In total, 487 loci, of which 434 are coding, have been annotated as part of the GENCODE reference set available from the UCSC browser. Comparison of GENCODE annotation with RefSeq and ENSEMBL show only 40% of GENCODE exons are contained within the two sets, which is a reflection of the high number of alternative splice forms with unique exons annotated. Over 50% of coding loci have been experimentally verified by 5' RACE for EGASP and the GENCODE collaboration is continuing to refine its annotation of 1% human genome with the aid of experimental validation.

UniPathway: a resource for the exploration and annotation of metabolic pathways.

UniPathway (http://www.unipathway.org) is a fully manually curated resource for the representation and annotation of metabolic pathways. UniPathway provides explicit representations of enzyme-catalyzed and spontaneous chemical reactions, as well as a hierarchical representation of metabolic pathways. This hierarchy uses linear subpathways as the basic building block for the assembly of larger and more complex pathways, including species-specific pathway variants. All of the pathway data in UniPathway has been extensively cross-linked to existing pathway resources such as KEGG and MetaCyc, as well as sequence resources such as the UniProt KnowledgeBase (UniProtKB), for which UniPathway provides a controlled vocabulary for pathway annotation. We introduce here the basic concepts underlying the UniPathway resource, with the aim of allowing users to fully exploit the information provided by UniPathway.